Yue ZQ, Yuan YW, Xu HS, Li XQ, Gan JH, Zou YH, Fan LJ, Xin L. Tropomyosin 3 regulates tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma to promote malignant progression in gastric cancer. World J Gastroenterol 2026; 32(22): 117290 [DOI: 10.3748/wjg.v32.i22.117290]
Corresponding Author of This Article
Lin Xin, Academic Fellow, Chief Physician, FRCS (Gen Surg), Professor, Researcher, Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Donghu District, Nanchang 330006, Jiangxi Province, China. xindoctor0504@126.com
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Oncology
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Yue ZQ, Yuan YW, Xu HS, Li XQ, Gan JH, Zou YH, Fan LJ, Xin L. Tropomyosin 3 regulates tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma to promote malignant progression in gastric cancer. World J Gastroenterol 2026; 32(22): 117290 [DOI: 10.3748/wjg.v32.i22.117290]
World J Gastroenterol. Jun 14, 2026; 32(22): 117290 Published online Jun 14, 2026. doi: 10.3748/wjg.v32.i22.117290
Tropomyosin 3 regulates tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma to promote malignant progression in gastric cancer
Zhen-Qi Yue, He-Song Xu, Jin-Heng Gan, Yong-Hui Zou, Luo-Jun Fan, Lin Xin, Department of General Surgery, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
Yi-Wu Yuan, Department of Abdominal Surgery, Jiangxi Cancer Hospital, Nanchang 330006, Jiangxi Province, China
Xue-Qin Li, Department of Nursing, The Second Affiliated Hospital of Nanchang University, Nanchang 330006, Jiangxi Province, China
Co-first authors: Zhen-Qi Yue and Yi-Wu Yuan.
Author contributions: Yue ZQ and Yuan YW have played important role in the experimental design as co-first authors; Yuan YW and Xin L designed the research study; Yue ZQ, Xu HS, Li XQ, Gan JH, Zou YH and Fan LJ performed the research; all of the authors read and approved the final version of the manuscript to be published.
Supported by National Natural Science Foundation of China, No. 82573536 and No. 82360591; and Science and Technology Plan of Jiangxi Provincial Health and Wellness Committee, No. 202510043.
Institutional review board statement: The study was reviewed and approved by Institutional Review Board of the Second Affiliated Hospital of Nanchang University (No. 058).
Institutional animal care and use committee statement: All procedures animals were reviewed and approved by the Institutional Animal Care and Use Committee of the Nanchang Royo Biotechnology Co., Ltd. (No. RYE2025021202).
Conflict-of-interest statement: All authors declare no conflict of interest in publishing the manuscript.
ARRIVE guidelines statement: The authors have read the ARRIVE guidelines, and the manuscript was prepared and revised according to the ARRIVE guidelines.
Data sharing statement: All data generated or analyzed in this study are included in the published article. The dataset used or analyzed in this study can be obtained from the corresponding author upon reasonable request.
Corresponding author: Lin Xin, Academic Fellow, Chief Physician, FRCS (Gen Surg), Professor, Researcher, Department of General Surgery, The Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Donghu District, Nanchang 330006, Jiangxi Province, China. xindoctor0504@126.com
Received: December 5, 2025 Revised: February 15, 2026 Accepted: March 20, 2026 Published online: June 14, 2026 Processing time: 176 Days and 4.2 Hours
Abstract
BACKGROUND
Tropomyosin 3 (TPM3) has been implicated in the progression of several cancers; however, its specific role and underlying molecular mechanisms in gastric cancer (GC) remain unclear. The current research aimed to investigate the role of TPM3 in the onset and advancement of GC, along with the related molecular pathways.
AIM
To investigate TPM3’s role in enhancing GC malignancy and elucidates the underlying molecular mechanisms.
METHODS
TPM3 expression in GC tissues was evaluated using bioinformatics analysis. Protein expression levels were determined using western blotting, and mRNA levels were measured through quantitative real-time PCR. Cellular functional assays, including cell counting kit-8 assay, 5-ethynyl-2-deoxyuridine incorporation, colony formation, wound-healing, and transwell migration/invasion, were conducted to assess the effects of TPM3 and tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma (YWHAG) on GC cell proliferation, migration, invasion, and metastatic potential. Cell cycle progression and apoptosis were analyzed using flow cytometry. A subcutaneous xenograft model in nude mice was employed to assess the tumorigenic potential of GC cells, while a tail vein injection model was used to evaluate their invasive and metastatic potential in vivo.
RESULTS
TPM3 was significantly upregulated in GC tissues and cells, and its high expression correlated with poor patient prognosis. Silencing TPM3 markedly inhibited GC cell proliferation, invasion, and metastasis while promoting apoptosis. TPM3 interacted with YWHAG, and TPM3 knockdown reduced YWHAG expression. Notably, the inhibitory effects of TPM3 silencing on GC progression were partially reversed by overexpressing YWHAG, confirming YWHAG as a key downstream effector. Furthermore, TPM3 knockdown suppressed activation of the mitogen-activated protein kinase pathway in a YWHAG-dependent manner. In vivo experiments demonstrated that increased TPM3 expression significantly promoted GC tumor growth and metastasis, whereas silencing YWHAG effectively attenuated this effect.
CONCLUSION
TPM3 promotes GC progression by regulating YWHAG and activating the mitogen-activated protein kinase signaling pathway. These findings identify the TPM3/YWHAG axis as a potential therapeutic target for GC intervention.
Core Tip: In this study, we investigated the role of tropomyosin 3 (TPM3) in gastric cancer (GC). We found that TPM3 is highly expressed in GC tissues and is associated with poor prognosis. Mechanistically, TPM3 promotes GC cell proliferation, invasion, and metastasis through interaction with tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma and subsequent activation of the mitogen-activated protein kinase signaling pathway. Both in vitro and in vivo experiments demonstrated that the TPM3/tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein gamma axis plays a critical role in GC progression.
